1. Field of the Invention
The present invention relates to novel organ fibrosis inhibitors, including kidney fibrosis inhibitors, pancreas fibrosis inhibitors, lung fibrosis inhibitors, vascular vessel fibrosis inhibitors, skin fibrosis inhibitors, bone marrow fibrosis inhibitors, liver fibrosis inhibitors, and the like. The invention also relates to organ fibrosis inhibitors which can be orally given or orally ingested and to pharmaceutical agents for various organ diseases due to fibrosis, particularly pharmaceutical agents (medical products) for liver diseases such as liver fibrosis and cirrhosis and to food and drink products such as food products for health use and food products for sick individuals.
Additionally, the present invention relates to methods for suppressing organ fibrosis, including methods for the therapeutic treatment, amelioration, progress prevention and prophylaxis of diseases due to organ fibrosis in biological organisms. The present invention further relates to methods of producing such organ fibrosis inhibitors, including forms such as medical products and food and drink products, and a combination of the plural active ingredients as an organ fibrosis inhibitor or a combination thereof for use in the method for suppressing organ fibrosis in the case when these active ingredients are used, and the like.
2. Discussion of the Background
To date, no pharmaceutical agents (prophylactic, ameliorating and/or therapeutic agent) effective as an organ fibrosis inhibitor, particularly a pharmaceutical agent for liver diseases such as liver fibrosis and cirrhosis have been reported.
For example, cirrhosis is not only the terminal stage of chronic liver diseases such as viral or alcoholic hepatitis, but also progresses highly frequently to hepatocellular carcinoma. Therefore, the development of a direct therapeutic method for liver fibrosis as a cause of cirrhosis is desired, in addition to existing therapeutic methods for the complications (ascites, edema, encephalopathy, jaundice).
Liver fibrosis is thought to be an outcome of excess deposition of extracellular matrices such as collagen during the repair of liver tissue when the balance is lost between hepatocyte necrosis triggered by an external factor, such as a virus and alcohol, or an internal factor involving autoimmune abnormality, and liver regeneration to maintain liver functions. At the cellular level, hepatocyte disorders and necrosis activate Kupffer's cells, endothelial cells and the like, so that TNF-α, TGF-β, and PDGF are released from the activated Kupffer's cells and endothelial cells. It is considered that those factors then activate Hepatic stellate cells as the main factor of liver fibrosis, so that cellular growth and collagen synthesis are triggered.
Even in organs such as the lungs, kidneys, pancreas, and skin, similarly to the liver, it is believed that fibroblasts existing in the individual organs and stromal cells specific to the individual organs (kidney mesangial cells, pancreatic stellate cells, etc.) lapse into abnormal growth and extracellular matrix synthesis due to the stimulation by various cytokines, leading to the occurrence of organ fibrosis.
Therefore, the development of a pharmaceutical agent with a significant direct efficacy on liver fibrosis is needed. Additionally, the development of a pharmaceutical agent effective for the inhibition of fibrosis in various organs in addition to the liver is also needed.
Thus, there remains a need for agents and methods for inhibiting organ fibrosis.